Splenic Cytotoxicity during High Dose IL2 with Cyclophosphamide Therapy in Mice : Dichotomy between Short- and Long-term Assay

概要

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Immunosuppressive manipulation with cyclophosphamide (CP) protects mice from a lethal toxicity of interleukin 2 (IL2). This in turn allows administration of very high doses (otherwise LD_<100>) of IL2 creating a therapeutic synergism. In vivo IL2-activated cytotoxicity was determined during high dose-IL2/CP treatments using a murine bladder cancer (MBT-2) model. Effector cells were obtained from the spleens of tumor bearing mice, and ^<75>Selenium-methionine labelled MBT-2 cells were used for targets. In a 24-h assay, high dose-IL2 with CP treatment increased the splenic cytotoxicity 2.6 fold higher than conventional dose of IL2 alone. In a 4-h assay, however, the cytotoxicity activity seen in the IL2 alone control was higher than any IL2 plus CP treatment groups. The data suggest that the excessive dose of IL2 (in the presence of CP) selectively augumented lymphoid cell population (s) which require a 24-h assay to demonstrate lysis, and such cell population (s) may play an important role in the observed in vivo therapeutic synergism.
北里大学の論文
1990-08-31